Variant chr14-103532704-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_152307.3(TRMT61A):c.454C>T(p.Arg152Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,612,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R152H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

TRMT61A
NM_152307.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.05

Variant links:

Genes affected

TRMT61A (HGNC:23790): (tRNA methyltransferase 61A) Enables mRNA (adenine-N1-)-methyltransferase activity. Involved in mRNA methylation. Predicted to be located in nucleoplasm. Predicted to be part of tRNA (m1A) methyltransferase complex. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TRMT61A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38461536).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRMT61A	NM_152307.3 linkuse as main transcript	c.454C>T	p.Arg152Cys	missense_variant	3/4	ENST00000389749.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRMT61A	ENST00000389749.9 linkuse as main transcript	c.454C>T	p.Arg152Cys	missense_variant	3/4	1	NM_152307.3	P1
TRMT61A	ENST00000299202.4 linkuse as main transcript	c.160C>T	p.Arg54Cys	missense_variant	2/3	1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000122

AC:

AN:

245626

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133996

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000112

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000822

AC:

AN:

1460544

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726624

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000190

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000330

Hom.:

Bravo

AF:

0.0000227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

Eigen

Benign

-0.0067

Eigen_PC

Benign

-0.082

FATHMM_MKL

Benign

0.60

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.056

MetaRNN

Benign

0.38

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

MutationTaster

Benign

0.96

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.1

REVEL

Benign

0.079

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0020

Polyphen

0.98

Vest4

0.49

MVP

0.41

MPC

1.2

ClinPred

0.57

GERP RS

1.8

Varity_R

0.54

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over